In immunocontraception there are two important applications for devices that give sustained release of proteins. First, for active immunization with a sperm antigen, it is important that the sperm antigen be released for long periods in a mode that will enhance its immunogenicity. Second, for passive immunization with a human monoclonal antibody against sperm or zona pellucida protein, a device that provides long-term release of active antibody would be ideal. Such devices should allow longer and less variable periods of contraception than can be achieved by simple injection of the antigen or antibody. The central goals of this proposal are to develop and test such devices. For the purpose of active immunization, we have synthesized a class of bioerodible polymers from the non-peptide linking of L-tyrosine dipeptide derivatives. These polymers have been shown in our initial studies to have two advantageous properties. First, the devices will produce sustained, controlled release of antigen in vivo, thereby initiating antibody production and immunization of the animal against that antigen. Second, products formed during polymer hydrolysis will have an adjuvant effect on the immune response, thereby enhancing the level and duration of antibody production and improving the protection against subsequent challenges by that antigen. The main objectives of this proposed study for active immunization are: 1) to synthesize poly(iminocarbonates) composed of N- and C-terminal blocked derivatives of N-(L-tyrosyl)-L-tyrosine dipeptide monomer, and characterize them with regard to molecular weight, mechanical properties, surface properties, and degradation behavior, 2) to measure, by ELISA, antigen- specific antibody levels in the serum of mice immunized with human PH-20 released from polymers; 3) to alter release patterns from polymeric devices by varying formulation parameters or applying external ultrasound (which enhances polymer degradation and antigen release rate) and determine the effect of these changes on adjuvanticity; and 4) to apply the resulting information toward the development of a bioerodible polymeric device which releases antigen in a controlled, predictable manner and produces antibody levels comparable to or greater than those produced by injection vaccination with a standard adjuvant. For passive immunization, our aim is to develop lactic acid-glycolic acid copolymer devices releasing monoclonal antibodies (Mabs) to the zona pellucida. By direct injection into female mice of either IE-3 or IE-10, Mabs to mouse ZP-2 and ZP-3 respectively, Dean and coworkers obtained completely effective contraception that lasted from 12-80 days (1,2) We will test various devices releasing the Mabs to determine if we can achieve 100% effective contraception for longer times with less animal-animal variation.